Sirtuin Protein Linked to Longevity

Monday, February 27, 2012

A member of the celebrated sirtuin family of proteins has been shown to extend lifespan in mammals — although it’s not the one that has received the most attention and financial investment.

Sirtuin genes and the proteins they encode have intrigued many researchers who study ageing ever since they were first linked to longevity in yeast. Results published in Nature suggest that the overexpression of one gene, called sirtuin 6 (SIRT6), can lengthen lifespan in male mice by as much as 15.8%.

For years, another member of the family, SIRT1, has hogged much of the spotlightbecause it is the mammalian member of the sirtuin clan most closely related to the longevity-linked yeast gene. Some researchers speculated that SIRT1 may also boost lifespan in mammals, and that it was the target of resveratrol, a compound found in red wine that had been linked to a variety of health benefits.

Sirtuin fervour reached its height in 2008, when the London-based drug company GlaxoSmithKline paid US$720 million for a biotechnology company that was initially focused on finding SIRT1-activating compounds as possible treatments for type 2 diabetes. But since then, results suggesting that SIRT1 affects lifespan in the fruitfly Drosophila melanogaster and the nematodeCaenorhabditis elegans have been questioned. No effect of SIRT1 on longevity in mammals has been reported, although its expression is associated with a healthier metabolism in mice fed a high-fat diet. So no magic diet pills yet.

When mice expressed higher levels of SIRT6 the researchers found that longevity in female mice was unaffected by the excess protein, but that the median lifespan of male mice rose by 14.5% in one line of their transgenic mice and 9.9% in another.

Another measure of longevity, maximum lifespan (generally more valued by researchers into ageing because it is less likely to be affected by other factors such as changes in infant mortality), rose by 15.8% in the first line of mice, and 13.1% in the second, although the latter increase was not statistically significant.